Pain is considered to play a basic physiological role in the detection and localization of tissue damage or potentially damaging physiological processes. Pain has been broadly classified as somatogenic, where a physiological explanation can be found, or psychogenic, where the physiological explanation is not known (The Merck Manual of Diagnosis and Therapy).
One example of a somatogenic pain is neuropathic pain. Generally, neuropathic pain is described as a pain which results from a dysfunction in the central or peripheral nervous system (Tremont-Lukats, I. et al.; Woolf, C. and Mannion, R.).
The pain can be both chronic and acute, and can also be evoked by noxious stimuli, also referred to as hyperalgesia, or by non-noxious stimuli referred to as allodynia (Attal, N.). Allodynia and hyperalgesia can have mechanical causes (dynamic or static), or a thermal cause. Examples of neuropathic pain include: all the painful peripheral neuropathies and specifically diabetic peripheral neuropathy; postherpetic neuralgia; and trigemincal neuralgia. Trigeminal neuralgia, for example, is the most common neuralgic syndrome in the elderly. The initial drug of choice is carbamazepine. For other types of pain, such as postherpetic neuralgia and painful diabetic neuropathy, amitriptyline is most commonly used. Other types of somatogenic pain that may have neuropathic components include cancer pain, postoperative pain, low back pain, complex regional pain syndrome, phantom pain, HIV pain, arthritis (osteo-arthritis and rheumatoid arthritis) pain and migraines.
Pain may also be a symptom of headache disorders. Migraines constitute one of the four major categories of primary headaches (International Headache Society; Silberstein, S. D. et al.). The other three types of primary headaches are tension-type, cluster and a miscellaneous-type (International Headache Society; Silberstein, S. D. et al.). One current view is that there is a continuous spectrum of headache severity ranging from mild tension headaches to severe migraines. Others consider tension headaches and migraines to be distinct entities.
Migraines are considered to be a familial disorder characterized by periodic pulsatile headaches. (Principles of Neurology). Migraines are found in about 4% of the male population and 7% of the female population. Migraines can occur in the presence or absence of an aura. An aura is a complex of focal neurological symptoms which may precede or accompany a migraine attack (Silberstein, S. D. et al.). Auras can be characterized by visual, sensory, or motor phenomenon, and may also involve language or brainstem disturbances (Silberstein, S. D. et al.).
A major theory regarding the pain of migraines is that it stems from a form of sterile neurogenic inflammation (Moskowitz, M. A. and Cutrer, F. M.). The neurogenic inflammation results in the leakage of plasma proteins into the dura mater, which can be quantified by measuring the leakage of radioactive albumin (Suzzi, M. C. and Moskowitz, M. A.).
Drugs used in the treatment of headache disorders such as migraines originate from a broad range of different drug categories. These include: 5-hydroxytryptamine agonists (5-HT1 agonists); dihydroergotamine; ergotamine; anti-emetics; anxiolytics; non-steroidal anti-inflammatory drugs; steroids; major tranquilizers; narcotics; beta-blockers; calcium channel blockers; anti-depressants; and anti-epileptic drugs. However, not all of the drugs in these categories are truly effective. Considering all of the drugs which are effective, there is still a need for more efficacious drugs, as well as anti-migraine treatments with less side effects.
U.S. Pat. No. 5,585,358 describes a series of derivatives of valproic acid amides and 2-valproenic acid amides for the treatment of epilepsy and other neurological disorders. However, U.S. Pat. No. 5,585,358 does not teach or suggest the use of derivatives of valproic acid amides and 2-valproenic acid amides for the treatment or prevention of pain or headache disorders.